Increased aerobic glycolysis through β2 stimulation is a common mechanism involved in lactate formation during shock states

During septic shock, muscle produces lactate by way of an exaggerated Na+K+ adenosine triphosphatase (ATPase)-stimulated aerobic glycolysis associated with epinephrine stimulation possibly through beta 2 adrenoreceptor involvement. It therefore seems logical that a proportion of hyperlactatemia in low cardiac output states would be also related to this mechanism. Thus, in low-flow and normal-to-high-flow models of shock, we investigate (1) whether muscle produces lactate and (2) whether muscle lactate production is linked to beta 2 adrenergic stimulation and Na+K+-ATPase. We locally modulated the adrenergic pathway and Na+K+-ATPase activity in male Wistar rats' skeletal muscle using microdialysis with nonselective and selective beta blockers and ouabain in different models of rodent shock (endotoxin, peritonitis, and hemorrhage). Blood flow at the probe site was evaluated by ethanol clearance. We measured the difference between muscle lactate and blood lactate concentration, with a positive gradient indicating muscle lactate or pyruvate production. Epinephrine levels were elevated in all shock groups. All models were associated with hypotension and marked hyperlactatemia. Muscle lactate concentrations were consistently higher than arterial levels, with a mean gradient of 2.5 +/- 0.3 in endotoxic shock, 2.1 +/- 0.2 mM in peritonitis group, and 0.9 +/- 0.2 mM in hemorrhagic shock (P < 0.05 for all groups). Muscle pyruvate concentrations were also always higher than arterial levels, with a mean gradient of 260 +/- 40 mu M in endotoxic shock, 210 +/- 30 mu M in peritonitis group, and 90 +/- 10 mu M in hemorrhagic shock (P < 0.05 for all groups). Despite a decrease in blood flow, lactate formation was decreased by all the pharmacological agents studied irrespective of shock mechanism. This demonstrates that lactate production during shock states is related, at least in part, to increased Na+K+-ATPase activity under beta 2 Stimulation. In shock state associated with a reduced or maintained blood flow, an important proportion of muscle lactate release is regulated by a beta 2 receptor stimulation and not secondary to a reduced oxygen availability.